Microdialysis probe technology provides access to tissue interstitium for either sampling of diffusible tissue constituents or delivery of bioactive substances. However, the relationship of the probe perfusate concentrations to their tissue counterparts is a complex function of solute molecular weight, solute physicochemical properties, tissue properties, probe membrane properties, probe geometry and perfusion rate, and the trauma of probe insertion into the tissue. These dependencies are being studied in order to improve the quantitative usefulness of the technology. Applications in the brain are being pursued in connection with Parkinson's disease, AIDS, alcoholism and studies of drugs of abuse. Other applications involve various normal tissues and tumors. Endogenous solutes of interest include dopamine and quinolinic acid. Examples of exogenous substances employed are Zidovudine (AZT) and ethanol. Mathematical modeling is used to describe diffusive and convective solute transport within the probe and in surrounding tissue. Diffusive and convective permeabilities of probe membranes have been determined under well-characterized conditions in vitro. Validation experiments in animals (usually rats) involve quantitative autoradiography, histology, and chemical assay of tissue surrounding the probe, as well as measurement of probe perfusate concentrations. (This is a continuation of Intramural Research Project Z01-RR- 10276-10 BEI.)